The present invention is concerned with a process for preparing the R and S enantiomers of substituted dithioacetal quinolines via the enzymatic hydrolysis of a substituted dithioacetal quinoline prochiral diester to form the corresponding substituted dithioacetal quinoline chiral monoester from which these R and S enantiomers are formed.
The invention is also concerned with the direct enzymatic hydrolysis of a racemic mixture of a substituted dithioacetal quinoline monoester to yield the R enantiomer of the desired compound.
It has been known in the art to use enzymes to hydrolyze prochiral diesters to form the corresponding chiral monoester. Pig liver esterase has been shown to be an effective enzyme in hydrolyzing meso diesters and diacetates to produce chiral compounds from which the R and S enantiomers of a compound may be formed. Guanti et al., Tet. Lett., 4639-4642, (1986). Santaniello et al., J. Org. Chem. (1988), 53 1567-1569 discusses the enzymatic hydrolysis of prochiral 3-substituted glutarate diesters utilizing pig liver esterase to form the corresponding chiral monoester compounds. Whitsides et. al., Angew. Chem. Int. Ed. Engl. 24 (1985) 617-638 discusses generally the use of enzymes as catalysts in synthetic organic chemistry. The present invention provides a unique way of forming chiral dithioacetal quinoline monoesters by enzymatic hydrolysis of the corresponding prochiral diesters from which the R and S enantiomers of the dithioacetal quinoline monoester may be formed in high yields at low costs. The present invention also provides a process for synthesizing the R enantiomers of a substituted dithioacetal quinoline by a direct enzymatic hydrolysis of a racemic mixture of a substituted dithioacetal quinoline monoester. These are improvements over the prior processes used to produce these compounds.